The project proposes a series of simulation experiments designed to determine the power, robustness, and validity of recently developed methods of segregation and linkage analysis, and to use insights gained from these experiments to analyze pedigree data on blook pressure and other variables related to hypertension. A particular effort will be made to detect major genes in an attempt to analyze the genetic component of hypertension. The power, robustness, and validity of three genetic models will be considered: 1) the transmission probability model, 2) the mixed model which includes components for a major gene, polygenic inheritance and sibling environmental correlations, and 3) a combined model, i.e. a mixed model with the single locus component parameterized in terms of transmission probabilities. The robustness of each model will be considered with respect to the presence of environmental skewness and kurtosis, familial environmental correlations, and dominance or epistasis in the multi-locus (polygenic) component. In particular simulated data will be based on parameters obtained from actual hypertension data, so that valid and appropriate conclusions can be drawn from these experiments. Methods of segregation and linkage analysis that are powerful, and robust with respect to failures of assumptions (particularly those found in the actual hypertension data) will be applied to two sets of data provided by other investigators. The primary set of data comprises five large pedigrees ascertained through a single hypertensive proband. The second set of data will consist of approximately ten large pedigrees ascertained at random as part of the Bogalusa Heart Study. Long range objectives include 1) the dissection of the genetic component of hypertension with a view to the identification of individuals with a genetic predisposition for hypertension before those individuals become overtly hypertensive and 2) an ongoing evaluation of new methods in segregation/linkage analysis, used to illuminate the nature of genetic components.